title: Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma.
abstract: Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic disease with substantial morbidities. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D056905:Chromosome Breakpoints; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics* / Q000378:metabolism
chemical_list: D015514:Oncogene Proteins, Fusion; D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020813:Receptor, trkB; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf